Complete information regarding the neural mechanisms regulating pituitary secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin is still lacking, although it is well established that the central nervous system participates in the general regulation of reproductive function in man. The mammary gland, an integral part of the female reproductive system, is subject to these hormgnol control mechanisms for normal development and maintenance. Several studies have characterized the growth response of mammary tumors to hormonal alterations, however, few in-depth studies have dealt with the hypothalamic-pituitary control system during the induction and maintenance of mammary neoplasia. This study postulates that a fundamental change occurs in the hypothalamic control of anterior pituitary function during the initiation and development of a mammary tumor. The major objectives of this proposal are to examine the interrelationships between the hypothalamus, anterior pituitary, and gonads, in both normal animals and in animals during the induction of mammary cancer. Parallel experiments conducted in normal and neoplastic animals involve: (a) characterizing pituitary sensitivity to hypothalamic releasing-factors and synthetic LRF, (b) characterizing the gonadal steroid feedback mechanism, and (c) determining the level of secretion of hypothalamic releasing factors. Studies will employ direct pituitary portal vessel infusion of compounds, and hypophysial stalk blood collections for assessing hypophysiotropic activity. Peripheral blood levels of pituitary hormones and LRF are assayed by radioimmunoassay.